Lyme Disease

This week we discussed an interesting case of Lyme Disease in Morning Report.

Briefly, a middle-aged lady presented with signs and symptoms of meningitis following recent exposure (5-10 days prior) to a tic bite. The patient was at a cottage in southern Quebec when she found a tic on their leg. A rash developed at the site of the tic bite that had the classic appearance of erythma migrans (EM) (aka erythema chronicum migrans, ECM), which is pathgnomonic for early localized Lyme Disease. 

An interesting issue was raised with this case - can Lyme Disease present with meningitis? And if it does, at what stage might you expect to see this?

For this case, it is important to understand the stages of Lyme Disease, as features of Lyme infection present according to a specific timeline of the disease. Notably, earlier features do not necessarily have to appear in order for the later features of the disease to manifest. Also, in a quarter of cases, patient do not even recall having a tic bite.

Fun Fact - The northward spread of Lyme into southern Ontario and Quebec may be linked to warmer temperatures (i.e. Global Warming). (Lyme Disease is named after the town where the earliest cases were discovered - Lyme, Connecticut). See below for reference.

Here are the three stages of Lyme Disease:

1. Early Localized Disease:
- Marked by erythema migrans, seen in more than 80% of patients, appears within 1-2 weeks after exposure.
- EM is often described as an erythematous circular rash having a central clearing; however, it may be uniformly erythematous in up to 50% of patients, especially when the lesion is small.
- Multiple lesions may be present
- Additional features may include lethargy, headache, mild neck stiffness, myalgias, arthralgias, and lymphadenopathy. Rarely can it present as aseptic meningitis. More likely is that these symptoms are confused with meningitis.

2. Early Disseminated Disease
- Occurs weeks-months after exposure if early disease has gone untreated.
- In this phase, systemic features of the disease are seen:

- Therefore, neurological manifestations such as meningitis are far more likely to appear >2 weeks after exposure to the infection.

3. Late Disseminated Disease
- Defined by prominent worsening  neurological and MSK symptoms 
- MSK: Arthritis of one or more joints, often the knee
- Neurological: Persistent neuropathy, myelitis

Treatment

The treatment for Lyme Disease includes either doxycycline, amoxicillin, or cefuroxime. All are safe and effective for early Lyme disease. Treatment should be started on detection of EM lesions in the case of early disease. In disseminated disease, treatment is started on the basis of compatible clinical picture with serology.

Back to the case....
Our patient's LP showed few cells and normal protein. Therefore, her clinical picture was consistent with possible aspetic meningitis, and not due to direct infection of Lyme into the CSF. She was treated for her early localized disease with amoxicillin and improved rapidly with conservative management. 

An excellent NEJM article from 2014 summarizes the diagnosis and treatment of Lyme Disease.
Click here for an interesting paper suggesting that Global Warming is contributing to the spread of Lyme Disease.

Polyarthitis

Diagnosing Polyarthritis

This past week we discussed the approach to polyarthritis. Here are the key points to keep in mind:

Key Lessons:

1. History of the Arthritis

The pattern, timing, and location of the joints affected are key to determining a diagnosis. Establish whether the complaint is articular (pain in all directions of movement, pain on passive movement) or peri-articular (pain in some ranges of motion, no pain on passive movement). Establish whether the arthritis is inflammatory (morning stiffness, systemic symptoms, joint swelling, limited range of motion) or non-inflammatory. Document the affected areas carefully on a diagram, for example:

1. Symmetric large joint: Seronegative arthropathy, rheumatoid arthritis

2. Asymmetric oligoarthritis: Seronegative arthropathy, infectious, or crystal induced

3. Symmetric small and large joints (non-inflammatory): Osteoarthritis

4. Symmetric small and large joints (inflammatory): Seropositive arthropathy, psoriatic arthritis

2. Establish a Differential Diagnosis:

Inflammatory conditions:

Seropositive conditions: Rheumatoid Arthritis, MCTD, Systemic Lupus Erythematosus, DM/PM

Seronegative condtions (Spondyloarthritidies): Anklyosing Spondylitis, Reactive Arthritis, Psoriatic arthritis, and IBD associated.

Systemic vasculitis

Crystal disease

Non-Inflammatory:

Osteoarthritis

Hemochromatosis

Acromegaly

Infectious:

Bacterial: S. aureus, Group G strep, Neisserial infections

Viral: Rubella, Parvovirus, HIV, Hepatitis B/C

Tick borne disease: Lyme disease (Borrelia burgdorferi)

Rheumatic Fever

Endocarditis 

Other Rarer Inflammatory Causes

Sarcoidosis

Palindromic rheumatism

Serum sickness

3. Associated symptoms

In order to narrow down your differential diagnosis, inquire about associated (extra-articular) symptoms:

Seropositive Disease: Malar rash, photosensitive rash, oral ulcers, sicca symptoms, nodules, Raynaud's phenomenon

Seronegative Disease (Spondylarthritis): low back pain, uveitis, diarrhea, enthesitis, psoriatic plaques, dactylitis.

Infectious: diarrhea illness, recent STI, recurrent fevers, cellulitic rash.

Osteoarthritis: No associated or systemic symptoms.

4. Investigations

- Bloodwork: CBC (screen of inflammatory or systemic disorder), serum urate (if gout is suspected), creatinine and urea (can help establish systemic involvement of a disorder), rheumatologic tests such as complement/ANA/ANCA/ESR (should only be ordered if a rheumatologic condition are highly suspected).

- Arthrocentesis: Can very be very helpful in establishing a diagnosis if fluid is present in one of the affected joints. Would likely be helpful in an acute on chronic process

- Imaging: Plain films are helpful if process is longstanding and underlying changes have developed.

Resources;

Click here for a review article on polyarthritis from CMAJ in 2000.

Click here for a review article on polyarthritis and fever from the NEJM from 1994.